Cell adhesion and migration are tightly controlled by regulated changes in the actin cytoskeleton. Previously we reported that the TGFβ (transforming growth factor β) superfamily co-receptor, TβRIII (type III TGFβ receptor; also known as betaglycan), regulates cell adhesion, migration and invasion, and suppresses cancer progression, in part, through activation of the small GTPase Cdc42 (cell division cycle 42), and Cdc42-dependent alterations to the actin cytoskeleton. In the present study we demonstrate that TβRIII specifically promotes filopodial formation and extension in MCF10A and HMEC (human mammary epithelial cell) mammary epithelial cells. Mechanistically, cell-surface TβRIII and Cdc42 co-localize to filopodial structures and co-complex in a β-arrestin2-dependent, and a TβRI/TβRII-independent manner. The β-arrestin2-mediated interaction between TβRIII and Cdc42 increases complex formation between the Cdc42 effectors IRSp53 with N-WASP (neuronal Wiskott–Aldrich syndrome protein) to increase filopodial formation. We demonstrate a function link between filopodial structures and epithelial cell adhesion as regulated by the TβRIII–Cdc42 interaction. The present studies identify TβRIII as a novel regulator of IRSp53/N-WASP via Cdc42 to regulate filopodial formation and cell adhesion.
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Research Article|
July 26 2013
The type III TGFβ receptor regulates filopodia formation via a Cdc42-mediated IRSp53–N-WASP interaction in epithelial cells
Sun Young Oh;
Sun Young Oh
*Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, NC 27708, U.S.A.
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Erik H. Knelson;
Erik H. Knelson
†Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27708, U.S.A.
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Gerard C. Blobe;
Gerard C. Blobe
*Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, NC 27708, U.S.A.
†Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27708, U.S.A.
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Karthikeyan Mythreye
Karthikeyan Mythreye
1
*Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, NC 27708, U.S.A.
1To whom correspondence should be addressed at the present address: Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC 29208, U.S.A. (email Mythreye@sc.edu).
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Publisher: Portland Press Ltd
Received:
November 08 2012
Revision Received:
June 04 2013
Accepted:
June 10 2013
Accepted Manuscript online:
June 10 2013
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem J (2013) 454 (1): 79–89.
Article history
Received:
November 08 2012
Revision Received:
June 04 2013
Accepted:
June 10 2013
Accepted Manuscript online:
June 10 2013
Citation
Sun Young Oh, Erik H. Knelson, Gerard C. Blobe, Karthikeyan Mythreye; The type III TGFβ receptor regulates filopodia formation via a Cdc42-mediated IRSp53–N-WASP interaction in epithelial cells. Biochem J 15 August 2013; 454 (1): 79–89. doi: https://doi.org/10.1042/BJ20121701
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